• 약학회지
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• 제43권1호
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• pp.77-84
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural naringenin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Naringenin inhibited plaque formations of HSV-l and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-l with selectivity index (SI) of 19.1 than on HSV-2 with SI of 5.7 The combined antiherpetic effects of naringenin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of naringenin with acyclovir on HSV-l and HSV-2 showed more potent synergism with CI values of 0.28∼0.81 for 50%, 70%, 90% effective levels than those with vidarabine with CI values of 0.86-3.28.

• 생약학회지
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• 제29권4호
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• pp.277-282
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• 1998

In order to search for anti-Herpes simplex virus type 1(HSV-1) agents, we screened 80 specimens of Korean traditional medicine by SRB assay. The methanol extracts of Thujae orientalis Semen (Cupressaceae) showed strong anti-HSV activity among samples tested. From the butanol fraction of Thujae orientalis Semen anti-HSV-1 agent was isolated by chromatographic separation using Amberlite XAD-4 and Sephadex LH-20. The structure was elucidated by spectroscopic methods, and was identified as ${\beta}-sitosterol$ (compound I). Compound I exhibited anti-HSV-1 activity with $EC_{50}$ of 0.6 mg/ml and $CC_{50}$ of 5.99 mg/ml, respectively.

• Tuberculosis and Respiratory Diseases
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• 제49권3호
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• pp.298-309
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• 2000

연구배경 : 암 유전자치료에서 각광받고 있는 HSV-tk/GCV 전략의 항암효과에는 다음과 같은 장점들이 거론되고 있다 : 1) GCV 처리에 의한 암세포 직접살상효과 2) HSV-tk 이입된 세포에 의해서 HSV-tk 이입되지 않은 주변세포를 살상하는 bystander effect 3) 생체 내 bystander eff ect로 알려 진 anti-tumor immunity. Retrovirus와 adenovirus sequence를 이용할 경우 몇몇 세포주와 마우스에서 이들이 목적유전자의 발현을 억제할 수 있다는 것이 보고되고 있다. 본 연구에서는 retroviral나 adenoviral vector로 HSV-tk 유전자를 이입한 Lewis 폐암세포주와 폐암 마우스 모델을 통하여 HSV-tk/GCV 전략의 장점을 조사하였고 이 viral vector들 사이의 차이를 비교 조사하였다. 또한 Lewis 폐암세포주에서 butyrate를 처리한 후 HSV-tk 유전자의 발현증가를 관찰하였다. 방법 : Lewis retroviral vector와 adenoviral vector로 HSV-tk 유전자를 이입한 후 butyrate로 HSV-tk 유전자의 발현을 유도하고 Western blotting수행하여 분석하였다. 생체 외에서 HSV-tk/GCV에 의한 세포살상효과를 MTT 검사로 수행하였고 생체 내에서 LLC 나 HSV-tk 이입된 LLC 세포주를 이식하여 종양소멸 및 bystander effect를 조사 하였다. 결과 : 1. Butyrate로 HSV-tk adenovirus로 이입된 LLC에서 증가한 반면 retrovirus로 이입된 LLC에서는 증가하지 않았다. 2. 생체 외 그리고 생체 내에서 viral vector로 HSV-tk를 이입한 종양세포에 GCV 투여하는 것은 종양 세포의 살상에 효과적이었으며 LLC와 LLC-tk 세포주를 혼합한 실험에서 bystander effect도 종양세포의 성장을 억제하는 것으로 관찰되었다. 결론 : 향후 생체 외 그리고 생체 내 실험에서 adenoviral vector를 이용한 유전자 전달에 butyrate를 함께 사용하면 유전자발현을 증진시킬 것으로 사료되며 자살 유전자인 HSV-tk을 종양에 이입하여 GCV을 처리 하는 치료가 폐암유전자치료에 효과가 있을 것으로 생각된다.

• IMMUNE NETWORK
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• 제15권2호
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• pp.91-99
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• 2015

Herpes simplex virus (HSV) is a common causative agent of genital ulceration and can lead to subsequent neurological disease in some cases. Here, using a genital infection model, we tested the efficacy of vinegar-processed flos of Daphne genkwa (vp-genkwa) to modulate vaginal inflammation caused by HSV-1 infection. Our data revealed that treatment with optimal doses of vp-genkwa after, but not before, HSV-1 infection provided enhanced resistance against HSV-1 infection, as corroborated by reduced mortality and clinical signs. Consistent with these results, treatment with vp-genkwa after HSV-1 infection reduced viral replication in the vaginal tract. Furthermore, somewhat intriguingly, treatment of vp-genkwa after HSV-1 infection increased the frequency and absolute number of $CD3^-NK1.1^+NKp46^+$ natural killer (NK) cells producing interferon (IFN)-${\gamma}$ and granyzme B, which indicates that vp-genkwa treatment induces the activation of NK cells. Supportively, secreted IFN-${\gamma}$ was detected at an increased level in vaginal lavages of mice treated with vp-genkwa after HSV-1 infection. These results indicate that enhanced resistance to HSV-1 infection by treatment with vp-genkwa is associated with NK cell activation. Therefore, our data provide a valuable insight into the use of vp-genkwa to control clinical severity in HSV infection through NK cell activation.

• Pediatric Infection and Vaccine
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• 제3권2호
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• pp.207-213
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• 1996

Herpes simplex virus(HSV) infections of the CNS are associated with significant morbidity and mortality even when appropriate antiviral therapy is administered. HSV infections of the brain can be subdivided into two categories : neonatal HSV infections, which usually are caused by HSV type 2, and herpes simplex encephalitis(HSE), which occur in patients over 3 months old and is nearly uniformly caused by HSV type 1. The clinical presentation of HSE is one of the focal encephalopathic process associated with altered levels of consciousness, fever, focal seizures and hemiparesis. But because of the lack of pathognomic clinical presentation and diagnostic procedure, the efforts to develop alternative diagnostic procedure have led to the use of new diagnostic technique such as polymerase chain reaction(PCR). We report a case of HSV type 1 encephalitis in 13 month old male infant who presented with altered level of consciousness, fever and focal seizures. With the use of the PCR, HSV-1 DNA was detected in cerebrospinal fluid from the patient. The symptoms and signs of encephalitis subsided by treatment with acyclovir in 14 days.

• 미생물학회지
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• 제42권3호
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• pp.177-184
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• 2006

항구 도시인 부산의 바이러스성 성병 감염 현황과 고위험군 지표로서 HPV, HSV 및 HBV 감염자의 성별, 연령대별 유형율 조사 등 기초자료를 확보하여 성매개감염증 사업관리 및 전파방지에 중요한 자료를 제공하고자 한다. 자궁경부도찰물 674건 중 HPV 23건(3.4%)과 HSV 1 2형 3건(0.4%) 9건(1.3%)이 각각 분리되었으며, 혈청 586건 중 HSV IgM 121건(3.6%), HSV-1 IgG 487건(83.1%), HSV-2 IgG 135건(23.0%), HBsAg 26건(4.4%), HBeAg 7건 (1.2%) 등이 검출되었다. HPV 유전자형별 분포도는 고위험군이 15종(13명), 저위험군이 6종(3명)으로 나타났으며, 복합감염은 7명이었다. 연령별 발생분포는 자궁경부도찰물의 경우 20대 이하가 24건(7.2%), 혈청의 경우 40대 이상이 101건(100%)으로 가장 높았다. 그리고 업소별 분포도는 자궁경부도찰물에서 보건소의 검진대상자(유흥업소종사자)들이 감염율이 가장 높았고, 혈청에서는 대용성병진료소의 검진대상자(특수업태부)가 감염율이 가장 높았다.

• 한국한의학연구원논문집
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• 제1권1호
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• pp.495-508
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• 1995

In order to search for anti-HSV agents from natural complex products, we extended the number of specimens. Both methanol extract and boiling water extract of the natural complex products were screened to detect anti-HSV activity by MTT assay. Anti-HSV activities of thirteen natural complex products extracted by methanol and boiling water were screened. Three of 13 natural complex products extracted by methanol showed efficacy against HSV. Natural complex products showing anti-HSV activities as methanol extracts were No.3, 6, 11 and their Sl were 323.809, 2811.041 and 708.20. As water boiling extracts, No.8 and No.11 have displayed Sl of 16.45 and 60.39 respectively. Especially anti-HSV activities of natural complex products extracted by methanol No.6 was stronger than other ones.

• 생약학회지
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• 제30권1호
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• pp.40-47
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural hesperetin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Hesperetin inhibited plaque formations of HSV-1 and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-2 with selectivity index (SI) of 9.8 than on HSV-1 with SI of 8.4. The combined antiherpetic effects of hesperetin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of hesperetin with acyclovir on HSV-1 and HSV-2 showed synergistic effects with CI values of $0.29{\sim}0.73$ for 50%, 70%, 90% effective levels and those with vidarabine showed partially synergistic or additive effects with CI values of $0.83{\sim}1.33$.

• 한국한의학연구원논문집
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• 제2권1호
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• pp.417-429
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• 1996

Herpes simplex viruses(HSV) are one of the most common infectious virus of man. Though chemotherapies and antibiotics against HSV have been developed in many countries, but anti-HSV agents were not satisfactory to mankind by their toxic reaction and side effects. In order to search for anti-HSV agents from Korean traditional prescriptions, we extended the number of specimens. Both methanol extract and boilling water extract of the Korean traditional prescriptions were screened to detect anti-HSV activities by MTT assay. Korean traditional prescriptions showing anti-HSV activities as methanl extracts were Paekyopsan, Chesupwilyungtang, Yongdamsagantang, and prescription 11. Four methanol extracts showing anti-HSV activities were freationated by hexane and their efficacies were tested. Hexane freationations of Paekyopsan, Chesupwilyungtang, and prescription 11 showed in anti-HSV activities both haxane and methanol fractionation.

• 대한미생물학회지
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• 제35권2호
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• pp.191-201
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• 2000

The viruses of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella-Zoster virus (VZV) which belong to the alpha herpes subfamily are important human pathogens. When eruptions were not fully developed from these viral infections, clinical diagnosis was not always easy and required virological confirmation test. The above viruses were reactivated in individuals who were compromised in immune competence for one reason or another. Polymerase chain reaction (PCR) enables rapid and sensitive detection of HSV and VZV DNAs. Its sensitivity was largely influenced by choice of primers. Authors conducted a study to detect of those three viruses in human specimens including vesicle fluid and joint fluid and serum using PCR methods. Primers used for this study were the general primer pair GPHV-RU which was known to amplify within the genes enjoying the highest degree of homology between UL15 of HSV and UL42 of VZV. PCR with primers hybridized pair GPHV-RU amplifies a 396 bp with THP-1 and HSV-2 standard strain DNA and 405 bp with VZV standard strain DNA. Restriction enzyme cleavage with HpaII and DdeI were used to detect and distinguish DNAs of THP-1 and HSV-2 and VZV. The purpose of this study was a rapid and easy detection of VZV and THP-1 or HSV-2 from various clinical specimens (vesicle fluid, serum and joint fluid) by PCR method. Used methods were: HSV PCR with primer 1, 2 and HpaII RE digestion; VZV nested PCR; HSV PCR with primer A, Band BssHII RE digestion. 1) In 33 cases (33/42, 78.6%) VZV was detected single or mixed infection from 42 clinical specimens which included vesicle fluid (5), serum form respiratory infected children (10), serum from immune suppressed adult cancer patients (7) and joint fluid from arthritis patients (20). 2) In 20 cases (20/42, 47.6%) HSV was detected singly or mixed infection and 19 of those cases were HSV-2 and 1 case was THP-1. 3) In 19 cases (19/42, 45.2%) VZV was singly detected which included serum from respiratory infected children (6 cases), joint fluid from arthritis patients (9 cases), vesicle fluid (2 cases) and serum form immunosuppressed cancer patients (2 cases). 4) HSV was singly detected in 6 cases (6/42, 14.3%) which included joint fluid from arthritis patients (5 cases) and serum form respiratory infected children (1 cases). 5) 14 cases of VZV and HSV mixed infection (14/42, 33.3%) were detected. They included vesicle fluid (3 cases), serum form immunosuppressed cancer patients (4 cases), serum from respiratory infected children (2 cases) and joint fluid from arthritis patients (5 cases). 6) HSV-1 and HSV-2 detection and typing by HSV PCR with primer A, Band BssHII RE digestion method was more sensitive and the results were easier to detect than on other method.